| Structural highlights
Publication Abstract from PubMed
Phospholipids are key components of cellular membranes and are emerging as important functional regulators of different membrane proteins, including pentameric ligand-gated ion channels (pLGICs). Here, we take advantage of the prokaryote channel ELIC (Erwinia ligand-gated ion channel) as a model to understand the determinants of phospholipid interactions in this family of receptors. A high-resolution structure of ELIC in a lipid-bound state reveals a phospholipid site at the lower half of pore-forming transmembrane helices M1 and M4 and at a nearby site for neurosteroids, cholesterol or general anesthetics. This site is shaped by an M4-helix kink and a Trp-Arg-Pro triad that is highly conserved in eukaryote GABAA/C and glycine receptors. A combined approach reveals that M4 is intrinsically flexible and that M4 deletions or disruptions of the lipid-binding site accelerate desensitization in ELIC, suggesting that lipid interactions shape the agonist response. Our data offer a structural context for understanding lipid modulation in pLGICs.
A lipid site shapes the agonist response of a pentameric ligand-gated ion channel.,Henault CM, Govaerts C, Spurny R, Brams M, Estrada-Mondragon A, Lynch J, Bertrand D, Pardon E, Evans GL, Woods K, Elberson BW, Cuello LG, Brannigan G, Nury H, Steyaert J, Baenziger JE, Ulens C Nat Chem Biol. 2019 Oct 7. pii: 10.1038/s41589-019-0369-4. doi:, 10.1038/s41589-019-0369-4. PMID:31591563[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Henault CM, Govaerts C, Spurny R, Brams M, Estrada-Mondragon A, Lynch J, Bertrand D, Pardon E, Evans GL, Woods K, Elberson BW, Cuello LG, Brannigan G, Nury H, Steyaert J, Baenziger JE, Ulens C. A lipid site shapes the agonist response of a pentameric ligand-gated ion channel. Nat Chem Biol. 2019 Oct 7. pii: 10.1038/s41589-019-0369-4. doi:, 10.1038/s41589-019-0369-4. PMID:31591563 doi:http://dx.doi.org/10.1038/s41589-019-0369-4
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